Efficacy and Safety of Nipocalimab vs Efgartigimod in a Randomized, Open-label, Phase 3b, Interventional Trial Including Within Class Switching From Efgartigimod to Nipocalimab

The primary objective is to evaluate the efficacy of nipocalimab versus efgartigimod in participants initiating neonatal Fc receptor (FcRn) treatment for generalized myasthenia gravis (gMG). This comparison is clinically relevant as both agents target the FcRn pathway to reduce pathogenic immunoglobulin G (IgG) antibodies in gMG, and establishing comparative efficacy will inform therapeutic decision-making for patients requiring FcRn inhibitor therapy.

The clinical trial enrolled a total of **30 participants** diagnosed with **generalized myasthenia gravis**. The study population included both **male** and **female** subjects aged **18 years or older** and younger than **75 years**. All participants were required to be **acetylcholine receptor (AChR) antibody positive**. Eligible individuals demonstrated a **Myasthenia Gravis Activities of Daily Living (MG-ADL) score** of at least 5, with a minimum of 50% attributed to non-ocular symptoms. The trial was divided into multiple arms with specific selection criteria: participants in arms 1 and 2 had a suboptimal response to current stable therapy as determined by the investigator and maintained **total immunoglobulin G (IgG)** levels of at least 6 g/L, while those in arm 3 had prior treatment experience with **efgartigimod** administered either intravenously or subcutaneously for at least one cycle and were considered appropriate candidates for switching to **nipocalimab** by both the participant and healthcare provider. The trial population represented individuals with **generalized Myasthenia Gravis** requiring evaluation of **neonatal Fc receptor (FcRn)** targeted therapy. No vulnerable populations were included in the study design.

This is a randomized, open-label, Phase 3b interventional trial evaluating the efficacy and safety of nipocalimab compared to efgartigimod alfa in participants with generalized myasthenia gravis. The study includes three arms, with Arms 1 and 2 comparing the two investigational medicinal products in participants initiating neonatal Fc receptor (FcRn) treatment, and Arm 3 assessing within-class switching from efgartigimod to nipocalimab. The trial is designed to evaluate the efficacy of nipocalimab versus efgartigimod in participants with gMG who have suboptimal response to current stable therapy. The study involves adult participants aged 18 years to less than 75 years who are acetylcholine receptor (AChR) antibody positive and have an MG-ADL score of at least 5 with at least 50% as non-ocular symptoms.

The primary endpoint is the averaged mean percent change from baseline in total IgG over Weeks 8 to 12 between Arms 1 and 2. Principal inclusion criteria for Arms 1 and 2 include total IgG levels of at least 6 g/L and suboptimal response to current stable therapy for generalized myasthenia gravis as determined by the investigator. For Arm 3, participants must have received treatment with efgartigimod administered intravenously or subcutaneously for at least one cycle, and both the participant and healthcare provider must agree that switching to nipocalimab is appropriate. The investigational medicinal products are administered via intravenous use, with nipocalimab as the test product formulated as a solution for injection and efgartigimod alfa as the comparator.

The maximum treatment period is 12 weeks for nipocalimab and 4 weeks for efgartigimod alfa. The estimated recruitment start date is February 4, 2026, with an estimated study completion date of April 30, 2027. Participants will undergo a series of study visits including a screening visit to assess eligibility criteria, treatment visits for administration of the investigational medicinal products, follow-up visits to evaluate efficacy and safety parameters, and an end-of-study visit. The duration of participant involvement will depend on the assigned treatment arm and adherence to the study protocol. Conditions that may lead to early termination from the study include withdrawal of consent, adverse events requiring discontinuation, protocol violations, or at the discretion of the investigator if continued participation is not in the best interest of the participant.

The experimental medication **nipocalimab** (sponsor product code JNJ-80202135) is administered as a **solution for injection** via **intravenous use**. The active substance is a protein classified as Protein - Other. The maximum treatment period is 12 weeks. Nipocalimab functions as a **neonatal Fc receptor (FcRn)** antagonist and serves as the test product in this clinical trial for participants with **generalized myasthenia gravis**.

The comparator medication **efgartigimod alfa** (also known by synonyms IMMUNOGLOBULIN G1, ANTI-(FCRN RECEPTOR) (HUMAN MONOCLONAL ARGX-113 FC FRAGMENT) and ARGX-113) is administered via intravenous use. The active substance is a protein classified as Protein - Other with EU substance number SUB198780 and **ATC code** L04AA58. The pharmaceutical form is identified as PHF00231MIG. The maximum treatment period is 4 weeks. Efgartigimod alfa has been designated as an **orphan drug** with designation number EU/3/18/1992 and serves as the comparator treatment in this randomized, **open-label**, phase 3b interventional trial. The study design includes evaluation of within-class switching from efgartigimod to nipocalimab.

The primary efficacy endpoint will assess the averaged mean percent change from baseline in total **IgG** levels over Weeks 8 to 12 between the nipocalimab and efgartigimod treatment arms. This endpoint will evaluate the comparative efficacy of nipocalimab versus efgartigimod in participants initiating neonatal Fc receptor (FcRn) treatment for **generalized myasthenia gravis**.